title: Six-month freedom from treatment failure is an important end point for acute GVHD clinical trials.
abstract: We studied the American Society for Blood and Marrow Transplantation (ASBMT) 6-month (m) freedom from treatment failure (FFTF) as a predictor of survival for patients with acute GVHD (aGVHD) requiring treatment. Adult patients undergoing allogeneic hematopoietic cell transplant (HCT) from February 2007 to March 2009 who were enrolled in a prospective biomarker clinical trial and developed aGVHD requiring systemic corticosteroids by day +100 were included (N=44). Six-month FFTF was defined as per the ASBMT guidelines (absence of death, malignancy relapse/progression or systemic immunosuppression change within 6 months of starting steroids and before chronic GVHD development). aGVHD was treated with systemic corticosteroids in 44 patients. Day 28 response after steroid initiation (complete response+very good partial response+partial response) occurred in 38 (87%) patients, but only 28 (64%) HCT recipients met the 6-m FFTF end point. Day 28 response predicted 6-m FFTF. Achieving 6-m FFTF was associated with improved 2-year (y) OS (81% vs 48%; P=0.03) and decreased 2-y non-relapse mortality (8% vs 49%; P=0.01). In multivariate analysis, 6-m FFTF continued to predict improved OS (hazard ratio, 0.27; P=0.03). The 6-m FFTF end point measures fixed outcomes, predicts long-term therapeutic success and could be less prone to measurement error than aGVHD clinical response at day 28.
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sengsayadeth
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: B N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Jagasia
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Goodman
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Greer
authors.affiliation: Department of Biostatistics, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chinratanalab
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Kassim
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Engelhardt
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000379:methods; D017211:Treatment Failure; D016896:Treatment Outcome